THE GASTROINTESTINAL TRACT (GIT)

Objectives:

• Functional anatomy of the GIT

• Functions of the GIT secretions of
mouth, stomach, duodenum, liver, and
jejunum
• Hormones of the GIT
• Absorption in various sections of GIT

1
THE GASTROINTESTINAL TRACT (GIT)
4
 Alimentary Canal

The alimentary tract provides the body with a

continual supply of water, electrolytes, vitamins,
and nutrients. To achieve this requires:

• Movement of food through the alimentary canal

• Secretion of digestive juices and digestion of food
• Absorption of water, electrolytes, and digestive
products
• Circulation of blood through GI organs to carry away
absorbed substances
• Control of all these by local, nervous and hormonal
systems
 Alimentary Canal

1. The GI tract is a tube subdivided into regions that

serve different functions associated with digestion and
absorption.
2. The lining of the GI tract is subdivided into layers:
mucosal, submucosal, and muscle layers.
3. There are three major control mechanisms: hormonal,
paracrine, and neural.
4. The innervation of the GI tract is particularly
interesting because it consists of two interacting
components: extrinsic and intrinsic.
A. Extrinsic innervation (cell bodies outside the wall of GI tract)
consists of two subdivisions of ANS:
parasympathetic and sympathetic.
Both have an important sensory (afferent) component.

B. Intrinsic (Enteric Nervous System) (cell bodies in wall of GI

tract) can act independently of extrinsic neural innervation.

5. When a meal is in different regions of tract, sensory

mechanisms detect presence of nutrients and mount appropriate
physiological responses in that region of tract, as well as in more
distal regions. These responses are mediated by endocrine,
paracrine, and neural pathways.
While the amount and function of the different layers
vary depending on the area of the GIT, the general
structure is the same along its entire length: the
innermost mucosal layer; the submucosal layer;
muscularis externa; and outer serosa.

The mucosal layer is present throughout the entire

GIT, but varies in structure depending on the
function of the particular section. In the mouth,
esophagus, rectum and anus, there can be
considerable abrasion. The mucosal layer is made
up of stratified squamous cells and is 10-15 cells
thick. In the jejunum, ileum and colon, it is a single
cell thick, and comprised of columnar cells.

9
 Physiologic Anatomy of the Gastrointestinal Wall

• Next slide shows a typical cross section of the

intestinal wall, including the following layers from
outer surface inward: (1) the serosa (2) a
longitudinal smooth muscle layer (3) a circular
smooth muscle layer (4) the submucosa and (5)
the mucosa. In addition, sparse bundles of
smooth muscle fibers, the mucosal muscle, lie in
the deeper layers of the mucosa. The motor
functions of the gut are performed by the
different layers of smooth muscle.
 Typical cross section of the gut

Regulation
1. Smooth Muscle Auerbach
2. GI Peptides
3. Nerves
Gastrointestinal Smooth Muscle Functions as a
Syncytium

• The individual smooth muscle fibers in the GI tract are

200 to 500 m in length and 2 to 10 m in diameter, and
they are arranged in bundles of as many as 1000 parallel
fibers.
• In the longitudinal muscle layer, the bundles extend
longitudinally down the intestinal tract; in the circular
muscle layer, they extend around the gut.
• Within each bundle, the muscle fibers are electrically
connected with one another through large numbers of
gap junctions that allow low-resistance movement of ions
from one muscle cell to the next.
• Therefore, electrical signals that initiate muscle
contractions can travel readily from one fiber to the next
within each bundle but more rapidly along the length of
the bundle than sideways.
 Membrane Potentials in Intestinal Smooth Muscle

Membrane potentials in intestinal smooth muscle. Note the slow waves, the
spike potentials, total depolarization, and hyperpolarization, all of which occur
under different physiologic conditions of the intestine.
 Neural Control of GI Tract

Intrinsic Control - Enteric nervous system

• Lies entirely wall gut from esophagus to anus
• ~ 100 million neurons (approximately equal to spinal cord)
a. Myenteric (Auerbach’s) plexus
b. Submucosal (Meissner’s) plexus
Location - gut wall from esophagus to anus
Composition - cell bodies, axons, dendrites, nerve endings
Innervation - gut cells, sensory nerves, other neurons
Integration - can occur entirely within ENS
- can function independent of ANS
Transmitters - many excitatory and inhibitory
Extrinsic Control - Autonomic Nervous System
- Parasympathetic - mainly stimulates (ACh)
- Sympathetic - mainly inhibits (NE)
 Neural Control of GI Tract

Neural control of the gut wall,

showing (1) the myenteric and
submucosal plexuses (black
fibers); (2) extrinsic control of
these plexuses by the
sympathetic and
parasympathetic nervous
systems (red fibers); and (3)
sensory fibers passing from the
luminal epithelium and gut wall
to the enteric plexuses, then to
the prevertebral ganglia of the
spinal cord and directly to the
spinal cord and brain stem
(dashed fibers).
 Intrinsic GI Nervous Control

Enteric Nervous System has two plexuses

1.Myenteric Plexus ‘Auerbach Plexus
• Outer area lying between longitudinal/circular muscle layers
• GI movement
• Linear chain entire length GI tract
• Controlling muscle movement along length of tract
• Not entirely excitatory
• Some neurons are inhibitory (↓sphincter tone)
2.Submucosal Plexus ‘Meissner’s Plexus
• Inner area lying in submucosa
• GI secretion and local BF
• Controlling function within inner wall gut
• Control local intestinal secretion, local absorption,
local contraction submucosal SM
Types of Neurotransmitters Secreted by Enteric Neurons
• More than a dozen different neurotransmitter substances
are released by the nerve endings of different types of
enteric neurons:

• (1) acetylcholine (2) norepinephrine (3) adenosine

triphosphate (4) serotonin (5) dopamine (6)
cholecystokinin (7) substance P (8) vasoactive intestinal
polypeptide (9) somatostatin (10) leu-enkephalin (11)
met-enkephalin (12) and bombesin (13).

• Acetylcholine most often excites gastrointestinal activity.

Norepinephrine almost always inhibits gastrointestinal
activity. This is also true of epinephrine, which reaches
the gastrointestinal tract mainly by way of the blood after
it is secreted by the adrenal medulla into the circulation.
The other aforementioned transmitter substances are a
mixture of excitatory and inhibitory agents
 Hormonal Regulation of GI Tract

• Endocrines (hormones)
- All GI hormones are peptides
- Released into blood  act on distant target cell

• Paracrines
- Some are peptides, some are not (histamine)
- Endocrine cells release  diffuse to target cells
- Can act on endocrine cells (stimulate or inhibit )

• Neurocrines (neurotransmitters)
- Some are peptides, some are not
- Nerves release  diffuse to target cells
 Hormonal Control of GI Motility

Hormone Source Stimulus Stomach Motility Pancreas

Gallbladder
Stomach Secretion
Secretin S cell acid entering Inhibits ↑HCO₃⁻
duodenum duodenum

CCK I cell fats/AA Inhibits ↑enzyme 1.contraction

duodenum entering emptying secretion 2. relaxation
duodenum sphincter Oddi

Gastrin G cells stomach Stimulates H⁺ *non-acid secreting

stomach distension stomach
antrum Parasym GRP Peptides (chronic gastritis)
duodenum inhibited by H⁺ ↓negative feedback
↑circulating gastrin
GIP/GDIP duodenum Fat/CHO Inhibits H⁺
K cells Amino acids ↓emptying **all first four
Motilin M Cells fasting ↑GI motility hormones stimulate
duod/jejun cyclical release ↓digestion insulin release
GI Paracrines
 GI Neurocrines

Peptide Location Action

VIP Gut mucosa, SM Relaxation gut SM
GRP (Bombesin) Gastric mucosa  Gastrin Release
Enkephalins Gut mucosa, SM  SM tone

VIP, vasoactive intestinal peptide,

GRP, gastrin-releasing peptide
 GI Peptides

Two structurally related families

• Gastrin and CCK
- 5 C-terminal AA identical
- Produce all effects of each other at high doses

• Secretin, GIP (GDIP, GLIP), VIP, Glucagon

- some effects are shared

GLIP = Glucagon-Like Insulinotropic Peptide

GDIP = Glucose Dependent Insulinotropic Peptide
GIP = Gastric Inhibitory Peptide
VIP = Vasoactive Intestinal Peptide
CCK = Cholecystokinin
 Gastrin
• Molecular forms - G-17 (antrum), G-34, G-14
• G-34 (duodenum) is not a dimer G-17 (equipotent)

• All share same 4 C-terminal AA producing biologic activity

• Pentagastrin - 5 AA synthetic product

Gastrin Released from G cells in antrum and duodenum

- Stimuli - protein digestion products
- nervous, physical distention
- calcium, decaffeinated coffee, wine

- Inhibition - acidification of antrum

 GI Peptides

• Response to meal -
- Large amounts of G-17 released from antrum
- Small amounts of G-34 released from duodenum

• Gastric acid secretion

- 1,500 x more potent than Histamine

• Trophic activity
- ↑growth of oxyntic mucosa of stomach, duodenal
mucosa, and colon mucosa
- Surgical removal of antrum causes atrophy
- Patients with gastrin secreting tumors have
mucosal hyperplasia and hypertrophy
 Cholecystokinin, CCK

• Molecular form - 8-AA, 33-AA, 38-AA, 59-AA

- Synthesized as preprohormone, then cleaved to
form family of peptides
- 5 C-terminal AA identical to gastrin
Biological activity -
- Minimal active fragment - 7 C-terminal AA
- Produces all effects of gastrin at high doses

Released from I-cells in duodenum and jejunum

• Stimuli for release
- Fatty acids or monoglycerides (not triglycerides)
- peptides and single AA
- Acid (weak)
 Secretin

• Molecular form 27-AA peptide preprohormone

• Biological activity entire molecule is required
• 14 AA identical to Glucagon
• Released from S-cells of duodenal mucosa

↑ Acid duodenum (pH < 4.5)  ↑secretin

↑ Fatty acids in duodenum  ↑secretin

“Nature’s Antacid”
Secretin ↓gastric acid secretion (an enterogastrone)
Secretin ↑ pancreatic and bile bicarbonate secretion
Secretin  ↑pepsin secretion
Secretin  Trophic effect on exocrine pancreas
 GLIP, GIP

• Member of Secretin family

• GLIP, GDIP, GIP
- 9 AA identical to Secretin in kind and position

- Released from duodenum and proximal jejunum

- All major foodstuffs - fat must be hydrolyzed
- Oral glucose but not intravenous glucose

• Physiological effects -

- GLIP ↑ insulin release

- GLIP  ↓gastric acid secretion (enterogastrone)
 Motilin

• linear 22 AA peptide
• unrelated to other hormones

• Released from duodenum and proximal jejunum

during fasting at 100 min intervals
• Release is under neural control

• Stimulates upper G.I. motility

• Accounts for the migrating motility complex,
• “housekeeping contractions”
• Migrating motor complexes are waves of activity
that sweep through the intestines in a regular cycle
during fasting state.
THE GASTROINTESTINAL
TRACT (GIT)

Part II

29
 GI Secretions

Throughout the gastrointestinal tract, secretory glands serve two

primary functions:
• First, digestive enzymes are secreted in most areas of the
alimentary tract, from the mouth to the distal end of the ileum.
• Second, mucous glands, from the mouth to the anus, provide
mucus for lubrication and protection of all parts of the
alimentary tract.
• Most digestive secretions are formed only in response to the
presence of food in the alimentary tract, and the quantity
secreted in each segment of the tract is usually the precise
amount needed for proper digestion.
• Furthermore, in some portions of the gastrointestinal tract, even
the types of enzymes and other constituents of the secretions
are varied in accordance with the types of food present.
• The purpose of this presentation is to describe the different
alimentary secretions, their functions, and regulation of their
production.
 Secretions of the GIT
There are 5 major secretory tissues in the GIT - the salivary glands, the
stomach, the pancreas, the hepatobiliary system and the intestine.

SALIVARY GLANDS: MUCUS, α-AMYLASE

STOMACH: HCl, PEPSINOGEN, MUCUS

LIVER: HCO3-, BILE SALTS + PIGMENTS
PANCREAS: HCO3-, ENZYMES
SMALL INTESTINE: ENZYMES
COLON: MUCUS
 Daily Secretion of GI Juices

Daily Volume (ml) pH

Saliva 1000 6.0-7.0
Gastric secretion 1500 1.0-3.5
Pancreatic secretion 1000 8.0-8.3
Bile 1000 7.8
Small intestinal secretion 1800 7.5-8.0
Brunner’s gland secretion 200 8.0-8.9
Large intestinal secretion 200 7.5-8.0
Total 6700
Alpha-Amylase initiates the digestion of
carbohydrates. But it's effectiveness depends on
how quickly the food passes to the acidic stomach.
The degree of efficiency of the enzyme also
depends on how well it disperses into the food and
how fast it is inactivated in the stomach. Estimates
vary depending on the nature of the food from 5-
50% efficiency.

The amylase found in saliva is also called ptyalin.

The rate of inactivation depends on the pH and the
amount of substrate. Both starch and its products
are able to partially protect it against inactivation by
gastric acid.
SALIVARY
AMYLASE

34
C-R' C-R'
C-R'' C-R'' + R'''
LINGUAL LIPASE
C-R''' C-OH

35
 Mechanism of GI Secretion
Regulation Glandular Secretion by Hormones
• Hormones liberated in response to local stimuli
 released into blood and carried to glands where they
stimulate secretion
• Chemically GI hormones are polypeptides or their
derivatives

Basic Mechanism of Secretion

1. Secretion of organic substance
2. Secretion of water and electrolytes to move substance
into target area
Typical function of a glandular cell for formation and secretion of enzymes
and other secretory substances.
© 2005 Elsevier
 Salivary Gland

Type of % of total
Gland saliva Secreted

Parotid Serous (ptylin;

alpha amylase) 90%
Submandibular Mucous (mucin)
/Serous

Sublingual Mucous 10%

/Serous

Buccal Mucous <1%

 Gastric Secretion

Oxyntic Gland: Consists of three types of cells

Mucous neck  mucus
Parietal Cell (oxyntic cell)
 HCL
 Intrinsic factor
80%
 Pepsinogen
 Rennin (chymosin)
Peptic Cell (chief cell) Gastrin
 Pepsinogen (small amounts)

Acetylcholine (parasympathetic) ↑pepsinogen (pepsin cells)

↑HCl (parietal cells)
↑Mucus (mucous cells)
Gastrin  ↑HCl (parietal cells but not affecting other cells)
Histamine  ↑HCl (parietal cells but not affecting other cells)
 PEPSINOGEN + HCl PEPSIN

N---VAL-LEU-ARG-TYR-TYR-ISO-LYS-GLY-PHE-MET---C

PEPSIN

N---VAL-LEU-ARG-TYR- -TYR-ISO-LYS-GLY-PHE-MET---C

40
C-R' C-R'
C-R'' C-R'' + R'''
GASTRIC LIPASE
C-R''' C-OH

41
 Regulation of GI Secretions

Gastric secretion is stimulated by neural, paracrine and endocrine

mechanisms
Acetylcholine - HCl secretion
- Mucus, Pepsinogen, and Gastrin
Histamine - HCl secretion
Gastrin - HCl secretion (1500 X > compared
histamine)

Gastric secretion is inhibited by:

Secretin
CCK
Somatostatin
GIP
Peptide YY (‘satiety hormone’ inhibits emptying)
 Pancreatic Enzymes

Proteolytic enzymes (for protein digestion)

- Trypsin
Cleave proteins to polypeptides
- Chymotrypsin
- Carboxypeptidase
Cleaves polypeptides to AA

Enzymes for carbohydrate digestion

• Pancreatic Amylase
- starches  disaccharides
- glycogen

Enzymes for fat digestion

• Pancreatic lipase - fat  fatty acids + monoglycerides
• Phospholipase - phospholipids  fatty acid
• Cholesterol Esterase - cholesterol esters  fatty acid
 PANCREATIC ENZYMES

PRECURSOR ENZYME FUNCTION

TRYPSINOGEN TRYPSIN PEPTIDE BONDS C
SIDE OF ARG/LYS
CHYMOTRYPSINOGEN CHYMOTRYPSIN PEPTIDE BONDS C
SIDE OF TYR/PHE
PROCARBOXYPEPTIDASE A C-PEPTIDASE A C TERMINAL
PEPTIDE BONDS
PROCARBOXYPEPTIDASE B C-PEPTIDASE B PEPTIDE BONDS C
SIDE OF ARG/LYS
PROELASTASE ELASTASE PEPTIDE BONDS
BY NEUTRAL AAS
PANCR. LIPASE TAGS
PHOSPHOLIPASES PGS
D/RIBONUCLEASE DNA/RNA
α-AMYLASE POLYSACCHARIDES
COLLAGENASE COLLAGEN
44
 N---VAL-LEU-ARG-TYR-TYR-ISO-LYS-GLY-PHE-MET---C

TRYPSIN,
CARBOXYPEPTIDASE B

N---VAL-LEU-ARG TYR-TYR-ISO-LYS GLY-PHE-MET---C

N---VAL-LEU-ARG-TYR-TYR-ISO-LYS-GLY-PHE-MET---C

CHYMOTRYPSIN

N---VAL-LEU-ARG-TYR-TYR ISO-LYS-GLY-PHE MET---C

45
 N---VAL-LEU-ARG-TYR-TYR-ISO-LYS-GLY-PHE-MET---C

CARBOXYPEPTIDASE A

N---VAL-LEU-ARG-TYR-TYR-ISO-LYS-GLY-PHE-MET--- C

N---VAL-LEU-ARG-TYR-TYR-ISO-LYS-GLY-PHE-MET---C

ELASTASE

N---VAL LEU-ARG-TYR-TYR-ISO-LYS GLY-PHE-MET---C

46
 N---VAL-LEU-ARG-TYR-TYR-ISO-LYS-GLY-PHE-MET---C

ALL PROTEASES

N---VAL LEU-ARG TYR-TYR ISO-LYS GLY-PHE MET--- C

47
C-R' C-OH
C-R'' C-R'' + R'+ R'''
PANCREATIC LIPASE
C-R''' C-OH

PANCREATIC
AMYLASE

48
 Bile Secretions

Bile Secretion: Liver normally secretes 600-1000 ml/d

Bile acids:

•Emulsify large fat particles to small particles where surface

areas can be attacked by lipase enzyme
•Aid in absorption of digested fat end products through
intestinal membrane
•Means of excretion of waste product
Bilirubin (end product hemoglobin destruction)
Cholesterol excess
50
 Bile Pigments

Bilirubin
• Lipid-soluble metabolite hemoglobin
• Gives golden-yellow color to bile
Stercobilin
• from metabolism of bilirubin by intestinal bacteria
• Gives brown color to feces

Secretin
• Stimulates pancreatic secretion almost entirely
NaHCO₃. Helps neutralize HCl from stomach
• Pancreatic secretion in turn stimulates ↑bile
secretion by bile ductules/ducts
 Small Intestine
Small Intestine
• Brunner’s glands secrete an alkaline mucus
 Compound mucus gland in duodenum
 Protects mucosal cells from acid chyme
 Stimulated by local irritation - Vagus (ACh)
 Inhibited by sympathetics (NE)

• Crypts of Lieberkühn - Intestinal secretion from crypts

~ 1800 ml/d almost all pure ECF with slightly alkaline pH
7.5-8
• Watery vehicle for absorption substances from chyme when it
comes into contact with villi
• Primary function small intestine is to absorb nutrients and digestive
products into blood
• Neurotransmitter secretagogues include VIP and Acetylcholine
 Small Intestine
• Enterocytes of mucosa (particularly those over villi) contain
digestive enzymes that digest specific foods while they are
being absorbed through the membrane
• Epithelial cells of deep crypt undergo continuous mitosis and
new cells migrate up and out of crypts replacing villus
epithelium  shed into intestinal secretions (life cycle ~ 5d)
Allows relativey rapid repair excoriations that occur in
mucosa
• Regulation of small intestine secretion is local enteric neural
reflexes particularly irritative/tactile from chyme
• Several peptidases for splitting small peptides  AA
• Sucrase, Maltase, Isomaltase, Lactase for splitting
disaccharides  monosaccharides
• Small amount intestinal lipase for splitting neutral fat 
glycerol and fatty acids
 Large Intestine

• Large intestine has many crypts of Leiberkuhn but no villi

• Epithelium secretes almost no digestive enzymes
• Contains mucous cells that secrete alkaline mucous
• Rate of mucous secretion is proportional to duct tactile
stimulation lining cells
• Stimulate pelvic nerves (parasympathetic distal ½-2/3rd
large intestine) ↑mucous and ↑peristalsis

Mucus
• Protects intestinal wall from excoriation
• Protects from bacteria in feces
• Alkaline pH ~ 8 to keep barrier from acids formed in feces